Phenylketonuira

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Summary

In this activity, students are assigned different alleles of the gene for phenylalanine hydroxylase to research using OMIM (Online Mendelian Inheritance in Man). Loss of this enzyme activity leads to accumulation of phenylalanine and the disease phenylketonuria (PKU). They are then asked to both explain and illustrate how this mutation may cause PKU.

The different alleles include point mutations, premature stop codons, frame shifts, deletions and loss of splice sites. By analyzing a specific allele, students are forced to follow the impact of the mutation through the DNA, RNA and protein. This exercise also illustrates that most genes have more than two alleles, in this case 67 have been identified.

Learning Goals

There are three goals of this exercise.

Students should be able to read a description of a mutation in a gene, and illustrate the impact of this mutation through DNA, RNA and protein.

Given the genetic code, students should be able to read aligned DNA and protein sequences to identify which codons and amino acids have been changed in an allele.

Given the properties of the amino acids, students should be able to explain how a specific mutation in DNA (genotype) would affect the encoded protein's activity (phenotype).

Context for Use

This exercise is designed for an introductory biology course, but could also be used in advanced high school courses, or college genetics courses. This is designed to be an out of class group activity, but could also be modified for individual students, or as an in-class activity. Students need a good understanding of the central dogma, mutations, protein structure and amino acid chemistry.

Description and Teaching Materials

In this activity students are assigned one of 11 different PKU alleles to research on OMIM. They are then asked to answer a few common questions about PKU, and some specific questions about their assigned allele. These answers are put into a provided powerpoint slide. The slides are then turned in, graded, and an example for each allele incorporated into the next lecture - this allows students to see each others work, and also uses student materials to teach them about 10 other alleles that can cause PKU.

The PKU student assignment contains detailed instructions, a link to OMIM, a copy of the genetic code, the aligned DNA and protein sequences of phenylalanine hydroxylase and the structures of the amino acids. A second file contains an answer key for the instructors, along with a suggested grading scale (in our class the assignment was worth 8 points).

The PKU powerpoint slide is given to the students for them to use in answering their questions, and to illustrate the affect of their mutation on the DNA, RNA and protein. The DNA sequence contains both exons and introns (which should be removed in the mRNA). Point mutations should be indicated at each step in the central dogma (i.e. ATG to AUG to Met) and an explanation of the possible impact of this mutation on enzyme activity provided. For other mutations that change the size of the DNA, mRNA or protein, these should also be illustrated graphically by removing exons, or truncating the protein. Examples from a few groups of students are provided to get a feel of what a correct project would look like.
PKU student assignment(Microsoft Word 366kB May31 06)PKU answer key(Microsoft Word 374kB May31 06)PKU powerpoint slide(PowerPoint 21kB May31 06)PKU sample student answers(PowerPoint 96kB May31 06)Assessment quiz(Microsoft Word 56kB May31 06)

Teaching Notes and Tips

We have used this activity in large undergraduate lecture settings, with 33 groups of 4 students. It is important to clearly explain what is expected of the students, as this activity gets to the core of several student misconceptions about the central dogma. Drawing an example on the board would be a good idea, but try to avoid giving away too much, i.e. the removal of introns, as these are concepts we want students to have to apply, not merely parrot back from what they saw in class. A week is plenty of time to accomplish this exercise, and it should be done after any lecture on the central dogma.

Assessment

The most direct form of assessment is grading the powerpoint slides that were turned in by the students.

A collection of quiz questions were also provided under teaching materials. These can be used as a pre-/post-quiz, or incorporated into an exam.